Importance of the -Aminobutyric AcidB Receptor C-Termini for G-Protein Coupling

Functional -aminobutyric acidB (GABAB) receptors assemble from two subunits, GABAB(1) and GABAB(2). This heteromeriza-tion, which involves a C-terminal coiled-coil interaction, en-sures efficient surface trafficking and agonist-dependent G-protein activation. In the present study, we took a closer look at the implications of the intracellular C termini of GABAB(1) and GABAB(2) for G-protein coupling. We generated a series of C-terminal mutants of GABAB(1) and GABAB(2) and tested them for physical interaction, surface trafficking, coupling to adenylyl cyclase, and G-protein-gated inwardly rectifying potassium channels in human embryonic kidney (HEK) 293 cells as well as on endogenous calcium channels in sympathetic neurons of the superior cervical ganglion (SCG). We found that the C-terminal interaction contributes only partly to the heterodimeri